TY - JOUR
A2 - Kleinjan, Alex
AU - Carrière, Virginie
AU - Arshad, Muhammad Imran
AU - Le Seyec, Jacques
AU - Lefevre, Benjamin
AU - Farooq, Muhammad
AU - Jan, Aurélien
AU - Manuel, Christelle
AU - Touami-Bernard, Laurence
AU - Lucas-Clerc, Catherine
AU - Genet, Valentine
AU - Gascan, Hugues
AU - Girard, Jean-Philippe
AU - Chalmel, Frédéric
AU - Lamontagne, Lucie
AU - Piquet-Pellorce, Claire
AU - Samson, Michel
PY - 2017
DA - 2017/05/21
TI - Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis
SP - 1359064
VL - 2017
AB - The alarmin IL-33 has been described to be upregulated in human and murine viral hepatitis. However, the role of endogenous IL-33 in viral hepatitis remains obscure. We aimed to decipher its function by infecting IL-33-deficient mice (IL-33 KO) and their wild-type (WT) littermates with pathogenic mouse hepatitis virus (L2-MHV3). The IL-33 KO mice were more sensitive to L2-MHV3 infection exhibiting higher levels of AST/ALT, higher tissue damage, significant weight loss, and earlier death. An increased depletion of B and T lymphocytes, NKT cells, dendritic cells, and macrophages was observed 48 h postinfection (PI) in IL-33 KO mice than that in WT mice. In contrast, a massive influx of neutrophils was observed in IL-33 KO mice at 48 h PI. A transcriptomic study of inflammatory and cell-signaling genes revealed the overexpression of IL-6, TNFα, and several chemokines involved in recruitment/activation of neutrophils (CXCL2, CXCL5, CCL2, and CCL6) at 72 h PI in IL-33 KO mice. However, the IFNγ was strongly induced in WT mice with less profound expression in IL-33 KO mice demonstrating that endogenous IL-33 regulated IFNγ expression during L2-MHV3 hepatitis. In conclusion, we demonstrated that endogenous IL-33 had multifaceted immunoregulatory effect during viral hepatitis via induction of IFNγ, survival effect on immune cells, and infiltration of neutrophils in the liver.
SN - 0962-9351
UR - https://doi.org/10.1155/2017/1359064
DO - 10.1155/2017/1359064
JF - Mediators of Inflammation
PB - Hindawi
KW -
ER -